Early development of the mammalian cerebral cortex proceeds via a sequence of proliferative and differentiative steps from neural stem cells toward neurons and glia. However, how these steps are molecularly orchestrated is still only partially understood. In this issue of The EMBO Journal, Artegiani and colleagues implicate Tox, a HMG‐box transcription factor previously known only for its role in lymphocyte development, in early cortical development.

Synopsis

Survival of mature murine B cells primarily depends of signals from the BCR and BAFF‐R. Downstream of the BCR, the kinase Syk plays a pivotal role in the activation of various cell survival pathways including the PI3K pathway. Our in vivo experiments show that a considerable fraction of mature Syk‐negative B cells can survive however they require BAFF receptor and CD19/PI3K signaling for their long‐term maintenance.

A fraction of mature B cells (˜25%) can be maintained in the absence of the kinase Syk over a prolonged time frame in spite of defective BCR signaling and the inability to activate the mTORC1 pathway in response to BCR ligation.

This maintenance is dependent on signals from the BAFF receptor since blocking of BAFF—BAFF‐R interaction results in decreased numbers of Syk‐deficient B cells.

Furthermore, the expression of the BCR coreceptor CD19, which upon phosphorylation by Syk promotes PI3K activation, is required for the survival of Syk‐deficient B cells.

The viability of CD19; Syk double‐deficient B cells is restored by the conditional ablation of FoxO1, the latter mimicking hyperactive PI3K activation.

This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs 4.0 License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

This paper ascribes a new role for Wnt4 in pre‐pubertal mammary gland development while revealing luminal cells to respond to Wnt activation. During regeneration, Wnt4 interacts with progesterone receptor signaling, correcting previous notions on RANKL signaling in this context.

Synopsis

This paper ascribes a new role for Wnt4 in pre‐pubertal mammary gland development while revealing luminal cells to respond to Wnt activation. During regeneration, Wnt4 interacts with progesterone receptor signaling, correcting previous notions on RANKL signaling in this context.

Wnt4 is an essential control factor for mammary epithelial stem cell function.

Cancer “stemness” and metastasis have been associated with EMT features, while defined molecular mechanisms remain scarce. This new study establishes an NFATc1–Sox2‐driven EMT program as crucial determinant for pancreatic cancer progression.

Synopsis

Cancer “stemness” and metastasis have been associated with EMT features, while defined molecular mechanisms remain scarce. This new study establishes an NFATc1–Sox2‐driven EMT program as crucial determinant for pancreatic cancer progression.

Cyclic GMP is the signal transducer of a family of transmembrane, particulate guanylyl cyclase (GC) receptors with key roles in physiology and disease. GC‐G, the last member of the membrane GCs identified in mammals, is an orphan receptor and its regulation and function have remained largely unknown. In this issue of The EMBO Journal, Chao et al (2015) show that the GC‐G/cGMP pathway, which is expressed in a specific cluster of olfactory neurons of neonatal mice, functions as a cold‐induced thermosensor, which triggers protective maternal care.

This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs 4.0 License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

The membrane‐spanning receptor guanylyl cyclase subtype GC‐G, specifically expressed in the Grueneberg ganglion neurons in the nose, is a novel thermosensor for cool ambient temperatures in mammals in vivo.

Synopsis

Many membrane proteins respond to extracellular ligands, but sensory nerves use specialized sensors also to report environmental temperatures. The transmembrane receptor guanylyl cyclase subtype GC‐G, expressed in Grueneberg ganglion neurons of the murine nose, is a novel type of molecular sensor for cool ambient temperatures in mammals.

GC‐G expression in mouse is confined to Grueneberg ganglion neurons of the murine nose.

Cool temperature stimulates the enzymatic activity of the GC‐G guanylyl cyclase by inducing its dimerization/oligomerization.

Independent of more classical sensors like the coolness‐activated TRPM8 ion channel, GC‐G is critical for coolness‐evoked ultrasound‐vocalization in abandoned mouse pups to elicit maternal‐care behaviors.